tbuckley/cabot-search huggingface dataset:
Deep learning on time series laboratory test results from electronic health records for early detection of pancreatic cancer.
Authors: Jiheum Park, Michael Artin, Kate E Lee, Yoanna S Pumpalova, Myles Ingram, Benjamin May, Michael Park, Chin Hur, Nicholas Tatonetti
Journal: Journal of Clinical Oncology (2022)

e16268 Background: Pancreatic cancer (PC) has a uniquely poor survival rate due to the absence of proven and effective methods for early detection. We thus aimed to leverage recent advances in deep learning towards the task of inferring early risk of PC from longitudinal laboratory test data contained within Electronic Health Records (EHR) data. Methods: In this study, we develop a novel deep learning framework for incorporating longitudinal clinical data from EHR to infer risk for PC. This framework includes a novel training protocol, which enforces an emphasis on early detection by applying an independent Poisson-random mask on proximal-time measurements for each variable. Data fusion for irregular multivariate time-series features is enabled by a “grouped” neural network (GrpNN) architecture, which uses representation learning to generate a dimensionally reduced vector for each measurement set before generating a final prediction. These models were evaluated using EHR data from Tripartite Request Assessment Committee (TRAC). Results: Our framework demonstrated better performance on early detection (AUROC 0.671, CI 95% 0.667–0.675, p &lt; 0.001) at 12 months prior to diagnosis compared to a logistic regression and a feedforward neural network baseline (black-box model). We demonstrate that our masking strategy results greater improvements at distal times prior to diagnosis, and that our GrpNN model improves generalizability by reducing overfitting relative to the feedforward baseline (Table). The results were consistent across reported race. Conclusions: Our study presents new approaches for integrating multimodal longitudinal clinical data with bias reduction strategies which results in improved early detection of PC. This study demonstrates for the first time the utility of multivariate time series laboratory test results for early detection of PC. Our proposed algorithm is potentially generalizable to improve risk predictions for other types of cancer and other diseases where early detection can improve survival. We split data into train set (80%) and hold-out set (20%) and presented mean AUROC and AUPRC with 95% confidence intervals.[Table: see text]
Axillary surgery after neoadjuvant chemotherapy in breast cancer patients downstaging from cN+ to ycN0.
Authors: Petr Krivorotko, Alexander Emelyanov, Alexander Komyahov, Elena Zhiltsova, Larisa Gigolaeva, Tengiz Tabagua, Kirill Nikolaev, Roman Pesotskiy, Viktoriia Gukova, Nikolay Amirov, Valentin Channov, Sergey Yerechshenko, Konstantin Zernov, Vladimir Semiglazov
Journal: Journal of Clinical Oncology (2022)

e12580 Background: Axillary lymph node dissection is a redundant method of surgical treatment and axillary staging for a large number of patients receiving neoadjuvant therapy with positive lymph nodes before NCT. Methods: The study included 212 patients with breast cancer (cT1-3N1M0) who received treatment at the breast tumors department of the N.N. Petrov NMRC of Oncology from 2019 to 2021 All patients included in the study had the cN1 initial status of the axillary lymph nodes. All patients underwent neoadjuvant systemic therapy and subsequent sentinel lymph node biopsy (SLNB). In patients with pathomorphologically proven metastatic lymph nodes (cN1) even at the initial diagnosis, lymph node marking was performed before the start of NCT and targeted axillary lymph node dissection after the completion of neoadjuvant systemic therapy. In the same patients, after SLNB and targeted axillary lymph node dissection, a complete (standard) axillary lymph node dissection was performed to determine the false-negative rate and the oncological safety of the procedure. Results: The identification rate of only one sentinel lymph node was 21% (40 out of 193 patients), two sentinel lymph nodes - 30% (58 out of 193 patients), more than 3 - 49% (95 out of 193 patients). When only 1 sentinel lymph node was found, the false-negative rate of SLNB was 20.0% (4 of 20) (95% CI, 5.7 to 43.7). When two sentinel lymph nodes were found, the false-negative rate of SLNB was 20.0% (6 of 30) (95% CI, 7.7 to 38.6). When three sentinel lymph nodes were found, the false negative rate of SLNB was 4.7% (2 of 43) (95% CI, 0 to 15.8). Among 45 patients who had a microseed with the iodine-125 radioisotope installed before the start of treatment, the frequency of identifying a marked node was 100%. In 19 patients, tumor cells were found in the lymph nodes. The false-negative rate of targeted axillary dissection in combination with SLNB was 5.3% (1 of 19) (95% CI, 0 to 26.0). Conclusions: Targeted axillary dissection and sentinel lymph nodes biopsy, provided that 3 SLNs are removed, are reliable methods for identifying patients in whom systemic therapy is guaranteed to achieve complete response of regional lymph nodes (ypN0), thereby relieving patients of the need to perform a crippling complete axillary lymph node dissection. Clinical trial information: 3/198.
Racial parity in esophageal cancer treatment at an integrated healthcare system.
Authors: Diana S. Hsu, Kian C Banks, Hyunjee V. Kwak, Amber Chang, Thach-Giao Truong, Jeffrey B. Velotta
Journal: Journal of Clinical Oncology (2022)

e16105 Background: This study evaluates survival outcomes of esophageal cancer patients treated at a large, tertiary care integrated healthcare system and whether there are differences based on race. Methods: We conducted a retrospective study from January 2010 to December 2019 among patients at Kaiser Permanente Northern California (KPNC). Self-reported racial ethnic groups included Caucasian, African American, Hispanic, Asian, and Other. Kaplan Meier and Cox regression analyses were used to evaluate differences in race, age, stage, and treatment utilization in relation to overall survival. Results: A total of 1,692 patients were diagnosed with esophageal cancer. Of these, 11% were Asian, 8.1% were Hispanic, and 6% were African American. Caucasians had the oldest mean age at diagnosis, 70.2 years, and the Hispanics had the youngest mean age at diagnosis, 64.6 years (p &lt; 0.001). There were no statistically significant differences in stage at time of diagnosis between race groups (p = 0.41). Adenocarcinoma was more common in Caucasians and Hispanics, while squamous cell was more common in African Americans and Asians (p &lt; 0.001). Treatments received by the patients included, surgery, chemotherapy, radiation, and a combination thereof (multimodal). There was no statistical significance among the races in treatment modalities received, including multimodal therapy (p = 0.12-0.66). The difference in mean overall survival (OS) between the race groups was not statistically significant. Kaplan-Meier survival analyses were performed and demonstrated statistically significant differences in mean OS between the two histologies, with adenocarcinoma having the highest survival of 33.9 months (p &lt; 0.001). Conclusions: We identified racial parity in survival outcomes and treatment utilization for esophageal cancer patients who were treated at a large integrated healthcare system where patients have equal access to care.[Table: see text]
Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line (1L) therapy for patients (pts) with advanced HER2-positive breast cancer: Preliminary results from a phase 1b/2 study.
Authors: Keun-Seok Lee, Xiaojia Wang, Young Hyuck Im, Xiaohua Zeng, Huiping Li, Kun Wang, Huiyan Li, Ping Zhou, Yuanyuan Bao, Zefei Jiang
Journal: Journal of Clinical Oncology (2022)

1031 Background: HER2-targeted agents have improved outcomes in HER2-positive breast cancer, but some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. In a Phase 1 trial (NCT02892123) zani was well tolerated and demonstrated preliminary antitumor activity as monotherapy/with chemotherapy in pts with pre-treated advanced HER2+ breast cancer. Methods: Cohort 1 of this ongoing open-label, Phase 1b/2 study (NCT04276493) is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ breast cancer who may have received prior neoadjuvant/adjuvant treatment. Cohort A pts received zani 30 mg/kg IV, Cohort B pts received zani 1800 mg IV, both with docetaxel 75 mg/m 2 IV Q3W. Primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS). Results: As of Nov 26, 2021, 25 pts with a median age of 57.0 years (range: 33.0–80.0) were assigned to Cohort A (n=11) or B (n=14). Median study follow-up was 7.0 months (range: 1.1–17.4) and the median number of treatment cycles was 10 (range: 2–20), 16 (64.0%) pts remained on treatment. Of the 22-efficacy evaluable (EE) pts, confirmed ORR was 86.4% (95% CI: 65.1, 97.1). The 6 months PFS rate was 90.9% (95% CI: 68.3, 97.7). Efficacy data are summarized in Table 1. All pts experienced ≥ 1 treatment emergent adverse event (TEAE) and 17 (68.0%) pts experienced ≥ Grade 3 TEAEs. In total, 23 (92.0%) pts experienced treatment related TEAEs (trTEAEs), and 17 (68.0%) pts experienced ≥ Grade 3 trTEAEs. The most common trTEAEs were diarrhea (56.0%) and decreased neutrophil count (52.0%). Serious trTEAEs occurred in two (8.0%) pts, trTEAEs leading to treatment discontinuation occurred in one (4.0%) pt and no trTEAEs led to death. Conclusions: Zani and docetaxel combination demonstrated antitumor activity in 1L therapy for advanced HER2+ breast cancer, with a manageable safety profile. Clinical trial information: NCT04276493. [Table: see text]
Diabetes impairs osteogenic differentiation of bone marrow mesenchymal stem cells
Authors: G Chiva-Blanch, G Arderiu, G Vilahur, L Badimon
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation (MICINN) Diabetes impairs osteogenic differentiation of bone marrow mesenchymal stem cells Background Diabetes is a severe metabolic condition that induces micro- and macrovascular disease, including atherosclerotic vascular disease, cutaneous lesions and bone necrosis. Whether it affects stem cell function is a matter of investigation. When the self-renewing capacity of mesenchymal stem cells (MSC) is compromised, their regenerative potential for cell therapy is impaired. Purpose We aimed to investigate the effects of diabetes on bone marrow- mesenchymal stem cells (BM-MSC) transcriptomics to evidence their potential for differentiation. Methods Bone marrow was extracted from femurs of Zucker rats, and BM-MSC were isolated by culturing adherent cells of extracted bone marrow in DMEM low glucose/ 20% FBS/ 1% P/S under hypoxic conditions (1% oxygen). After one week, MSC were characterized by flow cytometry. Gene expression arrays were used to analyse the expression of BM-MSC of Zucker rats with diabetes (ZD) compared to those of lean-normoglycemic controls (ZC) with the same genetic background (n=6). Results were analysed in silico to identify significantly modified signalling pathways. In addition, BM-MSC differentiation into endothelial, adipogenic and osteogenic cells was investigated in vitro. Results 95-99% of cells isolated from BM expressed CD90, a marker of MSC. Expression data analyses revealed a down-regulation of transcription factors related to the osteogenic pathway (Abcb1a, Adipoq, Fut1, Il1b, Kdr, Nes, Rhoa, Runx2, Tbx5, Tert and Tgfb3), and up-regulation of adipogenic- and angiogenic-related genes such as Bmp7, Casp3, Cd44, Csf2, Erbb2, Gdf7, Il10, Mcam, Nt5e, Pparg, Sox2, Vegfa and Vwf, in BM-MSC from animals with diabetes compared to lean controls. Concomitantly, BM-MSC from rats with diabetes showed impaired osteogenic differentiation in vitro compared to lean controls. No significant differences in adipogenesis or endothelial differentiation were observed between BM-MSC of rats with diabetes and lean controls. Conclusions Diabetes down-regulates several factors involved in the osteogenic differentiation pathway resulting in impaired osteogenesis. The imbalance in gene expression and MSC differentiation may partially explain the impaired regenerative capacity in diabetes.
Target vs. target plus standard biopsy in naïve patients: Results of a prospective randomized controlled trial
Authors: E. Checcucci, M. Manfredi, S. De Cillis, D. Amparore, F. Piramide, A. Piana, G. Volpi, M. Sica, P. Verri, S. Granato, M. Burgio, L. Ola, B. Carbonaro, D. Zamengo, A. Quarà, M. Della Corte, G. Busacca, P. Alessio, A. Pecoraro, I. Stura, G. Migliaretti, C. Fiori, S. De Luca, F. Porpiglia
Journal: European Urology (2022)
The role of FDG PET in the staging of bladder cancer patients candidate for radical cystectomy
Authors: L. Nocera, G. Basile, R. Leni, M. De Angelis, A. Martini, S. Scuderi, G. Gandaglia, A. Mottrie, A. Gallina, D. Raggi, L. Marandino, A. Necchi, F. Montorsi, A. Briganti, M. Moschini
Journal: European Urology (2022)
Novel PHB/PLA/TPS scaffold seeded by UDSCs as unique source for tissue engeneering in urethral repair
Authors: S. Žiaran, M. Culenova, M. Debreova, V. Smolinska, I. Bírova, P. Alexy, K. Topoliová, M. Klein, L. Danisovic
Journal: European Urology (2022)
EPEN-10. Elucidating the biological difference between pediatric supratentorial ependymomas using genetically engineered brain tumor organoids.
Authors: Mieke Roosen, Phylicia Stathi, Jens Bunt, Marcel Kool
Journal: Neuro-Oncology (2022)

Abstract Ependymomas (EPN) are neuroepithelial tumors of the central nervous system occurring both in adults and children. DNA methylation profiling has identified ten distinct molecular groups. In the supratentorial (ST) compartment, ZFTA-fusion positive and YAP1-fusion positive ST-EPN represent the two main groups in pediatric patients that are histologically very similar but have a completely different clinical behavior. While most ST-EPN-YAP1 patients survive, only 50% of ZFTA positive patients survive longer than 5 years. Improving survival of ZFTA positive patients requires better understanding of the tumor biology. Despite having different oncogenic fusions, it is unclear whether the cellular origin and tumor biology is related or not and why they respond differently to treatment. The development of human stem cell-derived brain organoids provides a novel opportunity to model these ST-EPN in vitro. These organoids mimic embryonal brain development, during which the cells-of-origin of ST-EPN as well as their micro-environment are present. To induce the development of ST-EPN in vitro, we genetically manipulated cerebral organoids to overexpress the group-specific oncogenic fusion proteins. Electroporating constructs expressing the different fusion proteins into organoids early in brain development (day 11), induced ectopic growth after approximately 30 days. Based on immunohistochemistry, we observed a different phenotype using either the ZFTA or YAP1 fusion constructs, as well as (over)expression of group-specific markers in the organoids. Preliminary transcriptomic analyses suggest that these genetically modified brain organoids represent models with features of human ST-EPN tumors. Ongoing single-cell RNA-sequencing and epigenomic analyses during normal organoid and tumor development will further reveal how well these models represent human primary tumors, how they develop in time, and possibly whether they originate from similar cells or different cells within these organoids. Hence, these models will uniquely contribute to the molecular and biological understanding of ependymomas and can be used to identify new targeted therapies.
Perioperative morbidity of surgical metastasectomy for renal cell carcinoma: An international multicenter study
Authors: E. Roussel, T.D. Lyon, V. Sharma, G. Carames, C.M. Lohse, S.A. Boorjian, R.H. Thompson, S. Joniau, M. Albersen, B.C. Leibovich
Journal: European Urology (2022)
Perceived risk of breast cancer and god health locus of control in high risk African American and caucasian women.
Authors: Minh-Tri Nguyen, Cheryl L. Thompson, Joy Knight
Journal: Journal of Clinical Oncology (2022)

e24142 Background: African American women are more likely than any other racial groups to present with a later stage of breast cancer. Survival rates among African American women with breast cancer are lower than that of their Caucasian counterparts. Studies have shown that women who believe that they can control their health through their own behavior may be more likely to report a lower perceived risk that women who believe that others (such as God or “powerful others” or chance) control their health outcomes. There is a limited body of literature on the effects of spiritual locus of health control and a patient’s perceived risk of breast cancer. Herein, we studied the association between God Locus of Health Control (GLHC) and perceived risk of breast cancer among 85 women recruited from a high-risk clinic. Methods: Consented participants that agreed to the study were asked to fill out the Patient Reported Outcomes Measurement Information Systems (PROMIS) initiative questionnaire. The PROMIS initiative standardizes measurements of psychosocial research in cancer to address major shortcomings in this field. The questionnaire includes demographic characteristics, perceived risk of breast cancer, and questions regarding spiritual and GLHC. Differences in patient demographics (including race), perceived risk, and multivariate testing was performed. Results: When asked to rank their chances of developing breast cancer in their lifetime, Caucasian participants were statistically more likely to respond with a higher perceived risk than African American participants (p = 0.01). Caucasian participants were more likely to respond with a higher perceived risk score when asked to compare their chances of developing breast cancer to that of the average woman their age (p = &lt; 0.001). Linear regressions correlating perceived risk, degree of GLHC and race did not show any statistical significance. Multivariate analyses only showed race was a statistically significant predictor of any of the perceived risk variables. Our study showed that Caucasian participants were more likely to have a lower GLHC score than their African American counterparts and were more likely to perceive a higher risk of developing breast cancer. GLHC was not statistically significantly associated with any of the 4 perceived risk measures (p &gt; 0.05 for all). Conclusions: Overall, there was not a statistically significant relationship between GLHC scores and perceived risk. Further larger-scale studies will be needed to further characterize these findings.
ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC
Authors: Christian Thomas, Aniello Federico, Susanne Bens, Mats Hellström, Olivera Casar-Borota, Uwe Kordes, Julia E Neumann, Matthias Dottermusch, Fausto E Rodriguez, Andrea C Lo, Sylvia Cheng, Glenda Hendson, Juliette Hukin, Christian Hartmann, Arend Koch, David Capper, Reiner Siebert, Werner Paulus, Karolina Nemes, Pascal D Johann, Michael C Frühwald, Marcel Kool, Martin Hasselblatt
Journal: Neuro-Oncology (2022)

Abstract Most atypical teratoid/rhabdoid tumors (ATRTs) occur in infants, but children and adolescents may also be affected. ATRTs occurring in older patients often comprise the molecular subgroup ATRT-MYC. Recently, central nervous system low-grade diffusely infiltrative tumor with INI1 deficiency (CNS LGDIT-INI1) has been described as a rare low-grade lesion (Nobusawa et al. Am J Surg Pathol 2020;44:1459-1468). Little is known on the molecular relationship of CNS LGDIT-INI1 and ATRT. We therefore further explored a series of six CNS LGDIT-INI1. The median age of the four males and two females was 16 years (range: 10-28 years). All tumors were of supratentorial location and showed low to moderate cellularity, diffuse growth of inconspicuous small SMARCB1-deficient tumor cells and reactive pleomorphic neuronal and glial cells with retained SMARCB1-staining in the background. In addition, two cases also displayed a high-grade rhabdoid component. After DNA isolation, purification and bisulfite conversion, samples were subjected to DNA methylation profiling (MethylationEPIC BeadChip array). Using DNA methylation-based classification and the Heidelberg Brain Tumor Classifier (version v11b4), all tumors were classified as ATRT-MYC (median calibrated score: 0.97). On t-SNE analysis, DNA methylation profiles grouped closely together in proximity to ATRT-MYC. Follow-up information was available for four cases (including the two cases with a high-grade component). Patients received heterogeneous treatments (including chemotherapy according to AT/RT protocols) and experienced stable disease or complete remission after an observation time of three to 56 months. In conclusion, CNS LGDIT-INI1 is a clinically and histologically distinct entity with relatively favorable outcome. Nevertheless, epigenetic similarity with ATRT-MYC and the potential of malignant progression warrants close follow-up examinations. In line with recent developments of WHO nomenclature, we propose to refer to these tumors as “low-grade diffusely infiltrative tumor, SMARCB1-mutant”.